The enzymes which synthesize and the metabolic pathways which utilize carbamylphosphate will be studied principally in mammals. The aim of the studies is to understand the regulation of the pathways, namely, arginine (and urea) and UMP biosynthesis. It is hoped that such studies for urea biosynthesis will be useful in acute ammonia intoxication. In the case of the UMP biosynthetic pathway, it is clear that the levels of these enzymes vary greatly due both to differentiation and development, so that tissues which divide rapidly such as cancers, regenerating and normal liver, brain, etc., have high levels of these enzymes. We would also like to see if the enzymes can be "induced" and "repressed", or if increased levels are merely the result for enzyme stabilization. Studies will involve purification and kinetic characterization of isolated enzymes of both pathways or the enzyme complexes of the UMP pathway, and studies on the in vivo metabolic control of these mammalian enzymes during growth, differentiation, or when changes in nutritional or hormonal states occur in normal individual as well as studies of abnormal tissues such as cancer or mutant cells. In addition, studies on the transport of dihydroorotate from the soluble cytoplasm into the mitochondria, and of orotate out of the mitochondria, will be undertaken. Former work on the aspartate transcarbamylases of Streptococcus faecalis and Citrobacter freundii will be continued, as well as work on the activator of the yeast carbonic anhydrase.